Impact of preterm birth on muscle mass and function: a systematic review and meta-analysis.

Individuals born preterm present lower exercise capacity. Along with the cardiopulmonary responses and activity level, muscle strength is a key determinant of exercise capacity. This systematic review aimed to summarize the current knowledge on the impact of preterm birth on skeletal muscle mass and function across the lifespan. The databases PubMed, MEDLINE, EBM, Embase, CINAHL Plus, Global Index Medicus, and Google Scholar were searched using keywords and MeSH terms related to skeletal muscle, preterm birth, and low birth weight. Two independent reviewers undertook study selection, data extraction, and quality appraisal using Covidence review management. Data were pooled to estimate the prematurity effect on muscle mass and function using the R software. From 4378 studies retrieved, 132 were full-text reviewed and 25 met the inclusion/exclusion criteria. Five studies presented a low risk of bias, and 5 had a higher risk of bias due to a lack of adjustment for confounding factors and presenting incomplete outcomes. Meta-analyses of pooled data from homogenous studies indicated a significant reduction in muscle thickness and jump test (muscle power) in individuals born preterm versus full-term with standardized mean difference and confidence interval of - 0.58 (0.27, 0.89) and - 0.45 (0.21, 0.69), respectively.    Conclusion: Overall, this systematic review summarizing the existing literature on the impact of preterm birth on skeletal muscle indicates emerging evidence that individuals born preterm, display alteration in the development of their skeletal muscle mass and function. This work also highlights a clear knowledge gap in understanding the effect of preterm birth on skeletal muscle development. What is Known: • Preterm birth, which occurs at a critical time of skeletal muscle development and maturation, impairs the development of different organs and tissues leading to a higher risk of comorbidities such as cardiovascular diseases. • Preterm birth is associated with reduced exercise capacity. What is New: • Individuals born preterm display alterations in muscle mass and function compared to individuals born at term from infancy to adulthood. • There is a need to develop preventive or curative interventions to improve skeletal muscle health in preterm-born individuals.

HAPI Fit: An Exercise Intervention to Improve Peak Aerobic Capacity in Young Adults Born Very Preterm.

INTRODUCTION: Individuals born preterm have reduced aerobic capacity, which could be related to impaired organ development. Their capacity to improve aerobic capacity with exercise training could therefore be limited, but this remains unknown. We aimed to test an exercise intervention to improve cardiorespiratory fitness in adults born preterm. METHODS: Twenty-one very preterm and 37 full-term individuals aged 18-33 yr took part in a 14-wk supervised exercise intervention of cardiovascular, resistance, and flexibility training (two group and one individual sessions per week). Adherence and compliance to intervention were recorded. Primary outcome was change in peak oxygen consumption (peak V̇O 2 ) measured before and after the intervention. Within- and between-group differences were estimated using nonparametric tests. RESULTS: Of 219 eligible individuals, 58 were enrolled and 14 participants dropped out over the course of the intervention. Among the 44 who completed the intervention, mean adherence was 82% and 66% for group and individual sessions, respectively. Compliance with training requirement varied between 71% and 100%. There was no difference in adherence between the preterm and full-term groups. Because only one preterm male met the adherence criteria, subsequent analyses were done exclusively on females. Both the term and preterm groups achieved higher peak V̇O 2 after the intervention [term = +4.2 (SD 4.3) mL·min -1 ·kg -1 , P < 0.01; preterm = +4.7 (2.9) mL·min -1 ·kg -1 , P < 0.01]. There was no between-group difference in the response to the intervention ( P = 0.729). CONCLUSIONS: Recruitment and adherence to an exercise intervention are challenging. Results could indicate improvements in cardiorespiratory fitness in young women born preterm after current exercise program. Adaptation of this intervention is needed for wider uptake.

High Amino Acid Intake in Early Life Is Associated With Systolic but Not Diastolic Arterial Hypertension at 5 Years of Age in Children Born Very Preterm.

BACKGROUND: The life course of individuals born very premature is a topic of increasing concern. The association between high early amino acid intake and later high blood pressure (HBP) in preterm neonates is debated. METHODS AND RESULTS: In a national, prospective, population-based birth cohort, EPIPAGE-2 (Etude Epidémiologique sur Petits Ages Gestationnels), we assessed blood pressure at 5 years. Eligible infants were those born between 24 and 29 weeks of gestation. Infants were distributed in 2 groups of 717 infants matched on propensity score on whether or not they were exposed to high amino acid intake (>3.5 g/kg per day at day 7); 455 control term infants were also enrolled. A value ≥95th percentile of reference values for age and height defined systolic or diastolic HBP. Blood pressure at 5 years of age was assessed for 389 and 385 children in the exposed and nonexposed groups, respectively. Rates (in percent) of systolic and diastolic HBP were 18.0% (95% CI, 14.5%-22.2%), 13.3% (95% CI, 10.3%-17.0%), 8.5% (95% CI, 6.5%-11.1%), and 9.0% (95% CI, 6.6%-12.3%), 10.2% (95% CI, 7.5%-13.6%), and 5.4% (95% CI, 3.8%-7.6%) in exposed, nonexposed, and term-born groups, respectively. Exposure to high early amino acid intake and maximal serum creatinine (by 50 µmol/L) between day 3 and day 7 were 2 independent risk factors for systolic HBP (adjusted odds ratio [aOR], 1.60 [95% CI, 1.05-2.43] and aOR, 1.59 [95% CI, 1.12-2.26], respectively) but not for diastolic HBP (aOR, 0.84 [95% CI, 0.50-1.39] and aOR, 1.09 [95% CI, 0.71-1.67], respectively). After adjustment for 5-year weight Z score, the aOR between high early amino acid intake and systolic HBP was 1.50 [95% CI, 0.98-2.30]. CONCLUSIONS: These results suggest that mechanisms of childhood systolic HBP involve neonatal renal challenge by high amino acid intake or dysfunction.

White matter microstructure is differently associated with executive functioning in youth born with congenital heart disease and youth born preterm.

INTRODUCTION: Executive function deficits and adverse psychological outcomes are common in youth with congenital heart disease (CHD) or born preterm. Association white matter bundles play a critical role in higher order cognitive and emotional functions and alterations to their microstructural organization may result in adverse neuropsychological functioning. This study aimed to examine the relationship of myelination and axon density and orientation alterations within association bundles with executive functioning, psychosocial well-being, and resilience in youth with CHD or born preterm. METHODS: Youth aged 16 to 26 years born with complex CHD or preterm at ≤33 weeks of gestational age and healthy controls completed a brain MRI and self-report assessments of executive functioning, psychosocial well-being, and resilience. Multicomponent driven equilibrium single-pulse observation of T1 and T2 and neurite orientation dispersion and density imaging were used to calculate average myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index values for eight bilateral association bundles. The relationships of bundle-average metrics with neuropsychological outcomes were explored with linear regression and mediation analyses. RESULTS: In the CHD group, lower MWF in several bundles was associated with poorer working memory and behavioral self-monitoring and mediated self-monitoring deficits relative to controls. In the preterm group, lower NDI in several bundles was associated with poorer emotional control and lower MWF in the left superior longitudinal fasciculus III mediated planning/organizing deficits relative to controls. No significant relationships were observed for psychosocial well-being or resilience. CONCLUSION: The findings of this study suggest that microstructural alterations to association bundles, including lower myelination and axon density, have different relationships with executive functioning in youth with CHD and youth born preterm. Future studies should aim to characterize other neurobiological, social, and environmental influences that may interact with white matter microstructure and neuropsychological functioning in these at-risk individuals.

Cardiopulmonary response to exercise in adults born very preterm.

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O2 consumption (peak VO2) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg-1 lean body mass·min-1) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO2 to work-rate relationship (ΔVO2/ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO2) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO2Results suggest limitations with peripheral O2 uptake in the muscle with reduced ΔVO2/ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O2 use during exercise are warranted to better understand mechanisms of exercise limitation.

The QTc-Bazett Interval in Former Very Preterm Infants in Adolescence and Young Adulthood is Not Different from Term-Born Controls.

INTRODUCTION: Although relevant for precision pharmacovigilance, there are conflicting data on whether former preterm birth is associated with QTc-Bazett prolongation in later life. METHODS: To explore QTc-Bazett interval differences between former preterm and/or extremely low birth weight (ELBW) cases and term-born controls in adolescence and young adulthood, we analyzed pooled individual data after a structured search on published cohorts. To test the absence of a QTc-Bazett difference, a non-inferiority approach was applied (one-sided, upper limit of the 95% confidence interval [CI] mean QTc-Bazett difference, 5 and 10 ms). We also investigated the impact of characteristics, either perinatal or at assessment, on QTc-Bazett in the full dataset (cases and controls). Data were reported as median and range. RESULTS: The pooled dataset contained 164 former preterm and/or ELBW (cases) and 140 controls born full-term from three studies. The median QTc-Bazett intervals were 409 (335-490) and 410 (318-480) ms in cases and controls. The mean QTc-Bazett difference was 1 ms, with an upper 95% CI of 6 ms (p > 0.05 and p < 0.01 for 5 and 10 ms, respectively). In the full dataset, females had a significantly longer QTc-Bazett than males (415 vs. 401 ms; p < 0.0001). CONCLUSIONS: QTc-Bazett intervals are not significantly different between former preterm and/or ELBW cases and term-born controls, and we rejected a potential prolongation > 10 ms in cases. When prescribing QTc-prolonging drugs, pharmacovigilance practices in this subpopulation should be similar to the general public (NCT05243537).

Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.

AIM: To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. METHODS: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), circulating leptin and adiponectin concentrations at age 2 years. RESULTS: HOMA-IR, HOMA-ß, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). CONCLUSION: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.

A comparison of altered white matter microstructure in youth born with congenital heart disease or born preterm.

Introduction: Alterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter - myelination, axon density, and axon orientation - in youth born with CHD or born preterm. Methods: Participants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations. Results: The CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group. Discussion: While youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches.

Associations between neurological examination at term-equivalent age and cerebral hemodynamics and oxygen metabolism in infants born preterm.

Background: Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA). Methods: Preterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA. Results: Steeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA. Conclusion: In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

Gratitude, fragility and strength: Perspectives of adults born preterm about prematurity.

AIM: The aim of the study was to explore how young adults thought that being born preterm had affected their lives. METHODS: Adult participants of a research cohort were questioned about their perspectives. Answers were analysed using mixed methods. RESULTS: Forty-five participants evaluated their health at median score of 8/10. When asked about the meaning of being born preterm, 65% had positive self-centred answers, invoking two main themes: being stronger/'a fighter'/more resilient and being a survivor/chosen; 42% also reported negative themes, such as having health problems and a difficult start. All heard about their prematurity from their parents, 55% with positive child-centred or healthcare system-centred themes, 19% with neutral themes; 35% also heard negative parent-centred themes (tragic experience, guilt, mother's health). When asked which words were associated with prematurity, participants mainly chose positive words for themselves and their family, but more negative words for how the media and society depicted prematurity. Answers were not correlated with adverse objective health measures. CONCLUSION: Participants evaluated their health in a balanced fashion. Preterm-born adults often feel that they have experienced positive transformations as a result of their traumatic start. They often have feelings of gratitude and strength, independent of health problems.

Arterial Hypertension in Women: State of the Art and Knowledge Gaps.

Hypertension is the leading risk factor for cardiovascular disease and premature death among women globally. However, there is a fundamental lack of knowledge regarding the sex-specific pathophysiology of the condition. In addition, risk factors for hypertension and cardiovascular disease unique to women or female sex are insufficiently acknowledged in clinical guidelines. This review summarizes the existing evidence on women and female-specific risk factors and clinical management of hypertension, to identify critical knowledge gaps relevant to research, clinical practice, and women's heart health awareness. Female-specific risk factors relate not only to reproduction, such as the association of gynecological conditions, adverse pregnancy outcomes or menopause with hypertension, but also to the specific roles of women in society and science, such as gender differences in received medical care and the underrepresentation of women in both the science workforce and as participants in research, which contribute to the limited evidence-based, gender- or sex-specific recommendations. A key point is that the development of hypertension starts in young, premenopausal women, often in association with disorders of reproductive organs, and therefore needs to be managed early in life to prevent future cardiovascular disease. Considering the lower blood pressure levels at which cardiovascular disease occurs, thresholds for diagnosis and treatment of hypertension may need to be lower for women.

A handheld bioprinter for multi-material printing of complex constructs.

In situbioprinting-the process of depositing bioinks at a defected area, has recently emerged as a versatile technology for tissue repair and restorationviasite-specific delivery of pro-healing constructs. The ability to print multiple materialsin situis an exciting approach that allows simultaneous or sequential dispensing of different materials and cells to achieve tissue biomimicry. Herein, we report a modular handheld bioprinter that deposits a variety of bioinksin situwith exquisite control over their physical and chemical properties. Combined stereolithography 3D printing and microfluidic technologies allowed us to develop a novel low-priced handheld bioprinter. The ergonomic design of the handheld bioprinter facilitate the shape-controlled biofabrication of multi-component fibers with different cross-sectional shapes and material compositions. Furthermore, the capabilities of the produced fibers in the local delivery of therapeutic agents was demonstrated by incorporating drug-loaded microcarriers, extending the application of the printed fibers to on-demand, temporal, and dosage-control drug delivery platforms. Also, the versatility of this platform to produce biosensors and wearable electronics was demonstrated via incorporating conductive materials and integrating pH-responsive dyes. The handheld printer's efficacy in generating cell-laden fibers with high cell viability for site-specific cell delivery was shown by producing single-component and multi-component cell-laden fibers. In particular, the multi-component fibers were able to model the invasion of cancer cells into the adjacent tissue.

Physical activity levels, pulmonary function, and MRI in children born extremely preterm: A comparison between children with and without bronchopulmonary dysplasia.

INTRODUCTION: Children with a history of bronchopulmonary dysplasia (BPD) may have lower physical activity levels, but evidence to date is mixed. This study compared physical activity levels between children born extremely preterm with and without history of BPD, and examined their associations with pulmonary magnetic resonance imaging (MRI) and pulmonary function test (PFT) indices. METHODS: This multicentre cross-sectional study included children aged 7-9 years born extremely preterm, with and without BPD. Children wore a pedometer for 1 week, then completed the Physical Activity Questionnaire (PAQ), pulmonary MRI, and PFT. Spearman correlations and multivariable linear regression modeling were performed. RESULTS: Of 45 children, 28 had a history of moderate-severe BPD. There were no differences in any physical activity outcomes by BPD status. Higher average daily step count and higher average daily moderate-to-vigorous physical activity (MVPA) were each correlated with greater forced vital capacity (r = 0.41 and 0.58), greater MRI lung proton density at full expiration (r = 0.42 and 0.49), and lower lung clearance index (r = -0.50 and -0.41). After adjusting for MRI total proton density and BPD status, a 5% increase in forced expiratory volume at 1 s was associated with 738 (95% CI: 208, 1268) more steps per day and 0.1 (0.0, 0.2) more hours of MVPA, respectively. CONCLUSION: School-aged children born extremely preterm have similar physical activity levels to their peers, regardless of history of BPD. MRI and PFT measures suggestive of gas trapping and/or airflow obstruction are associated with lower physical activity levels.

Sleep-disordered breathing symptoms and their association with structural and functional pulmonary changes in children born extremely preterm.

This study aimed to evaluate symptoms of sleep-disordered breathing (SDB) among children born extremely preterm, with and without a history of bronchopulmonary dysplasia (BPD), including associations between sleep and respiratory symptoms, physical activity, pulmonary function, and pulmonary magnetic resonance imaging (MRI). This multi-center cross-sectional study enrolled children aged 7-9 years born extremely preterm with and without BPD. Participants completed the Pediatric Sleep Questionnaire (PSQ), the modified Epworth sleepiness scale, a respiratory symptom questionnaire, pedometer measurements, pulmonary function testing, and pulmonary MRI. Spearman's correlations and univariate and multivariable linear regression modelling were performed. Twenty-eight of 45 children included had a history of moderate-to-severe BPD. The prevalence of sleep-related symptoms was low, with the exception of hyperactivity and inattention. There were no differences in mean (SD) scores on sleep questionnaires in children with and without BPD (PSQ: 0.21 (0.13) vs 0.16 (0.14), p = 0.3; modified Epworth: 2.4 (2.4) vs 1.8 (2.8), p = 0.4). Multiple regression analyses examining difference in sleep scores between groups, adjusting for gestational age and intraventricular hemorrhage, found no statistical difference (p > 0.05). Greater daytime sleepiness was moderately correlated with FEV1%-predicted (r = - 0.52); no other moderate-strong associations were identified.  Conclusions: There was no evidence of clinically important differences in sleep symptoms between children with and without BPD, suggesting that sleep symptoms may be related to prematurity-related factors other than a BPD diagnosis, including airflow limitation. Further research is necessary to explore the relationship between sleep symptoms, airway obstruction, and neurobehavioral symptoms among premature-born children.  Trial registration: NCT02921308. Date of registration: October 3, 2016. What is Known: • Presence of bronchopulmonary dysplasia (BPD) may further contribute to the development of SDB, though its impact is not well-studied. • Premature-born children have a greater risk of lung structural and functional differences, including sleep-disordered breathing (SDB). What is New: • There was no difference in sleep symptoms between children with and without BPD, suggesting that sleep symptoms are related to other prematurity-related factors, such as airflow limitation. • Greater daytime sleepiness was correlated with lower FEV1 in our population, which reflects greater airflow limitation.

Cardiac-specific deficiency of 3-hydroxy-3-methylglutaryl coenzyme A lyase in mice causes cardiomyopathy and a distinct pattern of acyl-coenzyme A-related biomarkers.

Deficiency of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase (HL) is an autosomal recessive inborn error of acyl-CoA metabolism affecting the last step of leucine degradation. Patients with HL deficiency (HLD) can develop a potentially fatal cardiomyopathy. We created mice with cardiomyocyte-specific HLD (HLHKO mice), inducing Cre recombinase-mediated deletion of exon 2 at two months of age. HLHKO mice survive, but develop left ventricular hypertrophy by 9 months. Also, within minutes after intraperitoneal injection of the leucine metabolite 2-ketoisocaproate (KIC), they show transient left ventricular hypocontractility and dilation. Leucine-related acyl-CoAs were elevated in HLHKO heart (e.g., HMG-CoA, 34.0 ± 4.4 nmol/g versus 0.211 ± 0.041 in controls, p < 0.001; 3-methylcrotonyl-CoA, 5.84 ± 0.69 nmol/g versus 0.282 ± 0.043, p < 0.001; isovaleryl-CoA, 1.86 ± 0.30 nmol/g versus 0.024 ± 0.014, p < 0.01), a similar pattern to that in liver of mice with hepatic HL deficiency. After KIC loading, HMG-CoA levels in HLHKO heart were higher than under basal conditions, as were the ratios of HMG-CoA/acetyl-CoA and of HMG-CoA/succinyl-CoA. In contrast to the high levels of multiple leucine-related acyl-CoAs, biomarkers in urine and plasma of HLHKO mice show isolated hyper-3-methylglutaconic aciduria (700.8 ± 48.4 mmol/mol creatinine versus 37.6 ± 2.4 in controls, p < 0.001), and elevated C5-hydroxyacylcarnitine in plasma (0.248 ± 0.014 µmol/L versus 0.048 ± 0.005 in controls, p < 0.001). Mice with liver-specific HLD were compared, and showed normal echocardiographic findings and normal acyl-CoA profiles in heart. This study of nonhepatic tissue-specific HLD outside of liver reveals organ-specific origins of diagnostic biomarkers for HLD in blood and urine and shows that mouse cardiac HL is essential for myocardial function in a cell-autonomous, organ-autonomous fashion.

The Impact of COVID-19 on Maternal Mental Health during Pregnancy: A Comparison between Canada and China within the CONCEPTION Cohort.

The effect of the COVID-19 pandemic on maternal mental health has been described in Canada and China but no study has compared the two countries using the same standardized and validated instruments. In this study, we aimed to evaluate and compare the impact of COVID-19 public health policies on maternal mental health between Canada and China, as we hypothesize that geographical factors and different COVID-19 policies are likely to influence maternal mental health. Pregnant persons >18 years old were recruited in Canada and China using a web-based strategy. All participants recruited between 26 June 2020 and 16 February 2021 were analyzed. Self-reported data included sociodemographic variables, COVID-19 experience and maternal mental health assessments (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7) scale, stress and satisfaction with life). Analyses were stratified by recruitment cohort, namely: Canada 1 (26 June 2020-10 October 2020), Canada 2 and China (11 October 2020-16 February 2021). Overall, 2423 participants were recruited, with 1804 participants within Canada 1, 135 within Canada 2 and 484 in China. The mean EDPS scores were 8.1 (SD, 5.1) in Canada 1, 8.1 (SD, 5.2) in Canada 2 and 7.7 (SD, 4.9) in China (p-value Canada 2/China: p = 0.005). The mean GAD-7 scores were 2.6 (SD, 2.9) in China, 4.3 (SD, 3.8) in Canada 1 (p < 0.001) and 5.8 (SD, 5.2) in Canada 2 (p < 0.001). When adjusting for stress and anxiety, being part of the Chinese cohort significantly increased the chances of having maternal depression by over threefold (adjusted OR 3.20, 95%CI 1.77-5.78). Canadian and Chinese participants reported depressive scores nearly double those of other crises and non-pandemic periods. Lockdowns and reopening periods have an important impact on levels of depression and anxiety among pregnant persons.

Neurodevelopmental consequences of early plasma sodium changes in very preterm infants.

BACKGROUND: Sodium fluctuations in very preterm neonates and their neurodevelopmental consequences are not well described. METHODS: We assessed the changes in plasma sodium and glucose in the first days of life in very preterm neonates and studied the association of glucose-corrected plasma sodium fluctuations on neurodevelopmental outcomes. We included 147 consecutive neonates born before 29 weeks of gestation in our center and retrospectively obtained plasma sodium, glucose, and glucose-corrected sodium levels. Neurodevelopmental assessment was obtained from the Canadian Neonatal Follow-Up Network. RESULTS: Mean ± standard deviation of plasma sodium changes within the first 10 days of life were 16.2 ± 6.0, 14.8 ± 5.3, and 11.1 ± 5.2 mmol/l in neonates born ≤25, 25-26, and 26-27 weeks of gestation, respectively (p < 0.001). Non-steroidal anti-inflammatory drug administration was associated with larger plasma sodium fluctuation. Eighty-six percent had a known neurological status at 18 months. Higher fluctuations in glucose-corrected plasma sodium were associated with death or neurodevelopmental impairment at 18 months corrected age (B = 3.19, 95% CI [1.24, 5.14]), and this association remained after adjustment for gestational age (B = 2.1, 95% CI [0.16, 4.04]). CONCLUSIONS: Neonates born very preterm show fluctuations in glucose-corrected plasma sodium during the first days of life, which may increase the risk of death or developmental impairment. IMPACT: Risk factors and neurodevelopmental consequences of plasma sodium changes in early neonatal life of preterm infants are not well characterized. This study shows for the first time that glucose-corrected plasma sodium fluctuations within the first days of life are more severe in preterm infants receiving non-steroidal anti-inflammatory drugs (NSAIDs) and are associated with death or neurodevelopmental impairment at 18 months corrected age. Large plasma sodium and glucose fluctuations should be expected more often in preterm infants receiving NSAIDs and should be avoided.

Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Reshaping the Preterm Heart: Shifting Cardiac Renin-Angiotensin System Towards Cardioprotection in Rats Exposed to Neonatal High-Oxygen Stress.

BACKGROUND: Approximately 10% of infants are born preterm. Preterm birth leads to short and long-term changes in cardiac shape and function. By using a rat model of neonatal high-oxygen (80%O2) exposure, mimicking the premature hyperoxic transition to the extrauterine environment, we revealed a major role of the renin-angiotensin system peptide Angio II (angiotensin II) and its receptor AT1 (angiotensin receptor type 1) on neonatal O2-induced cardiomyopathy. Here, we tested whether treatment with either orally active compounds of the peptides Angio-(1-7) or alamandine included in cyclodextrin could prevent postnatal cardiac remodeling and the programming of cardiomyopathy induced by neonatal high-O2 exposure. METHODS: Sprague-Dawley pups were exposed to room air or 80% O2 from postnatal day 3 (P3) to P10. Neonatal rats were treated orally from P3 to P10 and assessed at P10 and P28. Left ventricular (LV) shapes were characterized by tridimensional computational atlases of ultrasound images in addition to histomorphometry. RESULTS: At P10, high O2-exposed rats presented a smaller, globular and hypertrophied LV shape versus controls. Treatment with cyclodextrin-Angio-(1-7) significantly improved LV function in the O2-exposed neonatal rats and slightly changed LV shape. Cyclodextrin-alamandine and cyclodextrin-Angio-(1-7) treatments similarly reduced hypertrophy at P10 as well as LV remodeling and dysfunction at P28. Both treatments upregulated cardiac angiotensin-converting enzyme 2 in O2-exposed rats at P10 and P28. CONCLUSIONS: Our findings demonstrate LV remodeling changes induced by O2-stress and the potential benefits of treatments targeting the cardioprotective renin-angiotensin system axis, supporting the neonatal period as an important window for interventions aiming at preventing cardiomyopathy in people born preterm.